The NET-PD program used a rational, scientific approach for the selection and evaluation of potential therapies for the prevention of Parkinson's disease (PD) progression. Since its original award, the NET-PD program has successfully completed two futility studies, known as Futility Study 1 (FS-1) and Futility Study 2 (FS-TOO) which evaluated the therapeutic potential of four compounds (creatine, minocycline, coenzyme Q10 (CoQ10), and GPI-1485) [5, 6]. The results of FS-1 and FS-TOO informed the design of a large, simple clinical trial for efficacy of creatine treatment in slowing clinical decline in participants with early, treated Parkinson's disease, known as LS1. LS1 is a multi-center. Phase 3, double-blind clinical trial of creatine for the prevention of PD progression that tests the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care.